Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

Breckpot, Karine; Aerts, Joeri L.; Thielemans, Kris

doi:10.1038/sj.gt.3302947

Cited by 104 publications

(96 citation statements)

References 182 publications

(167 reference statements)

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“…19 Several studies have shown that HIV-1-based lentivectors are able to deliver genes into non-dividing and less proliferating cells, including peripheral DCs. [20][21][22][23] One advantage of using the lentivector system is that the vector does not encode any major viral proteins. This eliminates the generation of competition of anti-vector responses, which competes with the generation of anti-transgene responses.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, lentivectors have thus been proposed to be an ideal vector tool for vaccine delivery. 20,[24][25][26][27][28][29][30][31][32][33] Based on the study of Sindbis virus, a member of the Alphavirus genus and the Togaviride family, we have reported a mutant Sindbis virus glycoprotein, (SVGmu) which can specifically bind to DC-specific intracellular adhesion molecule (ICAM) 3 grabbing non-integrin (DC-SIGN, CD209). 34 DC-SIGN is a C-type lectin-like receptor and is expressed on DCs and macrophages.…”

Section: Introductionmentioning

confidence: 99%

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Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Yang

Liang

et al. 2011

Cancer Gene Ther

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Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8 þ T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Yang

Liang

et al. 2011

Cancer Gene Ther

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“…[16][17][18] Direct injection of lentivectors into mice does transduce DCs, leading to antigen-specific CD8 + T cell responses and anti-tumor immunity. [19][20][21][22] However, these recombinant viral vectors usually have broad specificity and transduce multiple cell types. Development of viral vectors capable of transducing DCs in a cell-specific manner in vivo could potentially improve the safety and efficacy of vaccination.…”

mentioning

confidence: 99%

Engineered lentivector targeting of dendritic cells for in vivo immunization

et al. 2008

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We report a method of inducing antigen production in dendritic cells (DCs) by in vivo targeting with lentiviral vectors that specifically bind to the DC surface protein, DC-SIGN. To target the DCs, the lentivector was enveloped with a viral glycoprotein from Sindbis virus, engineered to be DC-SIGNspecific. In vitro, this lentivector specifically transduced DCs and induced DC maturation. A remarkable frequency (up to 12%) of ovalbumin (OVA)-specific CD8 + T cells and a significant antibody response were observed 2 weeks following injection of a targeted lentiviral vector encoding an OVA transgene into naïve mice. These mice were solidly protected against the growth of the OVA-expressing E.G7 tumor and this methodology could even induce regression of an established tumor. Thus, lentiviral vectors targeting DCs provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.Immunization is one of the most productive tools in modern medical practice yet it still has limitations and novel methods of immunization are likely to be needed. 1 One of the great advances in our understanding of the process of immunization was the recognition of the role of dendritic cells (DCs) as specialized antigen-presenting cells (APCs). 2 This has led to attempts at DC-based immunization/vaccination involving loading DCs with specific antigens. 3, 4 Although significant progress has been made on various aspects of this vaccination method, many challenges still remain in order to rationally manipulate DCs to achieve protective immunity. [3][4][5] There is growing interest in genetically modifying DCs to make them either express antigens or produce immuno-stimulatory molecules. 6 Of these methods, viral vectors have been proven most effective for the delivery of genes into DCs in vitro. 7 The most popular viral vectors capable of transducing and expressing transgenes in DCs are adenoviral vectors, 8-10 gammaretroviral vectors 11, 12 and lentiviral vectors. [13][14][15] Considerable effort has also gone towards direct immunization using recombinant viral vectors as vaccine carriers. In these protocols, viral vectors are injected directly into an animal with the hope that a fraction will target immune cells and stimulate the desired immunity. Direct injection of adenoviral vectors was shown to induce both innate and adaptive immune responses and is currently being evaluated as a subunit vaccine for several infectious diseases and cancer. 16-18 Direct injection of lentivectors into mice does transduce DCs, leading to antigen-specific CD8 + T cell responses and anti-tumor immunity. 19-22 However, these 4Correspondence should be addressed to D.B. (baltimo@caltech.edu) or P.W. (pinwang@usc.edu). 3 These authors contribute equally to this work. COMPETING INTERESTS STATEMENT:The authors declare that they have no competing financial interests. Here we report a new method of in vivo DC targeting through the DC-specific surface molecule called DC-SIGN (also known as CD209) ...

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“…Although scale up of the co-transfection approach remains a challenge, this method is versatile in allowing production of lentivectors which can be pseudotyped with a variety of viral proteins with different cell type tropisms (see reviews by 40,41 . Recombinant lentivector pseudotyped with envelope protein from different viruses results in preferential transductions of restricted cell types, enabling partial targeting.…”

Section: Lentivector Developmentmentioning

confidence: 99%

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Munn

Falo

2007

Expert Review of Vaccines

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SummaryEncouraged by remarkable successes in preventing infectious diseases and by the well established potential of immune system for controlling tumor growth, active therapeutic immunization approaches hold great promise for treating malignant tumors. In recent years, engineered recombinant viral vectors have been carefully examined as genetic immunization vehicles and have been demonstrated to induce potent T cell mediated immune responses that can control tumor growth. Very recent efforts suggest that lentivectors possess important advantages over other candidate recombinant viral vectors for genetic immunization. Here we review the development of recombinant lentivectors and the characteristics of T cell immune responses elicited by lentivector immunization, including the mechanism of T cell priming with a focus on the role of skin dendritic cells (DC) and potential applications for tumor immunotherapy.

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Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

Cited by 104 publications

References 182 publications

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Engineered lentivector targeting of dendritic cells for in vivo immunization

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

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